An increased body mass impairs vascular function (VF), an important characteristic of subjects suffering from type 2 diabetes and a risk marker for cardiovascular diseases. However, a wide variety of in vivo VF markers exists each measuring different aspects of VF. Each of these markers addresses a different aspect of the vasculature. Studies comparing under standardized conditions the differences and relationships of the many different VF measurements in lean and abdominally overweight / obese subjects are missing. Also, there is a great need to know which of these markers are sensitive to dietary challenges.

Therefore, it is imperative to conduct an extensive study on dietary effects and interrelationships of a broad spectrum of VF measurements and plasma biomarkers in lean and overweight / obese subjects. Focus will be on FMD, a well accepted biomarker for cardiovascular disease. The investigators propose to examine, in a two-way parallel-randomized human intervention study, the effects of weight-loss in abdominally overweight / obese men on VF markers and plasma biomarkers related to low-grade inflammation and vascular activity during the fasting and both the postprandial and hyperinsulinemic state. Furthermore, differences - and relations between - VF measurements and plasma biomarkers will be compared cross-sectionally between lean and abdominally overweight / obese male subjects.

Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:

Vascular activity: differences between lean and abdominally overweight / obese men and effects of weight loss [ Time Frame: Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline at 2 hours after meal consumption ] [ Designated as safety issue: No ]

Flow-mediated dilation (FMD) of the brachial artery.

Secondary Outcome Measures:

Vascular function markers related to the macrovasculature: differences between lean and abdominally overweight / obese men and effects of weight loss [ Time Frame: Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline during the postprandial (at 2 hours after meal consumption) / hyperinsulinemic state (at 2 hours after initiation of the clamp) ] [ Designated as safety issue: No ]

Vascular function markers related to the microvasculature: differences between lean and abdominally overweight / obese men and effects of weight loss [ Time Frame: Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline during the postprandial (at 1 and 3 hours after meal consumption) / hyperinsulinemic state (at 2 hours after initiation of the clamp) ] [ Designated as safety issue: No ]

Metabolic risk markers related to the metabolic syndrome: differences between lean and abdominally overweight / obese men and effects of weight loss [ Time Frame: Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline during the postprandial (during 4 hours after meal consumption) / hyperinsulinemic state (during 3 hours after initiation of the clamp) ] [ Designated as safety issue: No ]

Biomarkers for low-grade inflammation and endothelial activation.

Other Outcome Measures:

Body fat components and fat content of intra-abdominal organs: differences between lean and abdominally overweight / obese men and effects of weight loss [ Time Frame: Difference after weight-loss due to restriction of energy intake for 8 weeks ] [ Designated as safety issue: No ]

Blood pressure: difference between lean and abdominally overweight / obese men and effects of weight loss [ Time Frame: Difference after weight-loss due to restriction of energy intake for 8 weeks ] [ Designated as safety issue: No ]

A very-low energy diet (Modifast Intensive) for 4-5 weeks providing 2.1 MJ/day in order to reduce body weight. After 4-5 weeks a mixed solid energy-restricted diet up to 4.2 MJ/day with a recommended composition for the following 1-2 weeks. Then, a diet matching their energy requirements to maintain newly achieved body weights (weight-stable conditions) for at least 2 weeks.

Other: Weight-loss treatment

A very-low energy diet (Modifast Intensive) for 4-5 weeks providing 2.1 MJ/day in order to reduce body weight. After 4-5 weeks a mixed solid energy-restricted diet up to 4.2 MJ/day with a recommended composition for the following 1-2 weeks. Then, a diet matching their energy requirements to maintain newly achieved body weights (weight-stable conditions) for at least 2 weeks.

Active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident

Contra-indications for MRI imaging

Use of an investigational product within the previous 1-month

Not willing to give up being a blood donor (or having donated blood) from 8 weeks before the start of the study, during the study or for 4 weeks after completion of the study

Not or difficult to venipuncture as evidenced during the screening visit

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01675401